Excluding certain insects, humans are the Earth's supremely social species. Befitting this status, it is increasingly clear that social processes are a prime determinant of human health. Whether conceptualized as social integration or social support, positive social connectivity (PSC) has been shown in hundreds of studies to protect against illness development, to reduce morbidity once illness is established and to reduce mortality from an array of natural causes. Conversely, negative social processes (NSP)-whether measured as loneliness, social isolation or interpersonal conflict-predict disease development and concomitant increases in disease-related morbidity and mortality. The current proposal has been designed to identify behavioral and physiological mechanisms through which PCS/NSP interact with psychosocial stress to promote resilience in the context of illness, A central innovation of the current project is that assessments of social processes and stress reactivity will not rely on first person report, on generalizations across a number of circumstances or on retrospective reporting. Rather, PSC/NSP and stress reactivity will be assessed objectively-that is from a third person perspective-in real time and in specific situations. Similarly, rather than relying on the vagaries and complexities of natural disease processes to supply health-relevant behavioral outcomes, we model inflammation (a central element of all disease states) through the use of treatment with interferon (IFN)-alpha, which provides a standardized regimen of chronic cytokine exposure known to produce profound behavioral disturbances, including depression, fatigue and sickness, in a high percentage of individuals. To objectively assess social processes, the current project will employ the Electronically Activated Recorder (EAR), which periodically and unobtrusively records snippets of ambient sounds in people's momentary environments. Participants wear the device while going about their lives. In tracking moment-to-moment ambient sounds, it yields acoustic logs of their behaviors and interactions as they naturally unfold. To objectively assess behavioral and physiological responses to psychosocial stress the current project will employ the Trier Social Stress Test (TSST), a standardized laboratory stressor known to reliably activate behavioral, neuroendocrine and inflammatory responses. These novel methodologies and model systems will be employed to test the hypotheses that (a) pre-existing affiliative and prosocial behavior will promote resilience in the context of chronic inflammation and that (b) -conversely-chronic inflammation will reduce affiliative and prosocial behavior via effects on stress reactivity, neuroendocrine function and sleep. Finally, it will explore (c) the potential mediating role of stress physiology. To test these hypotheses, 120 subjects with chronic hepatitis C virus infection will be randomized to receive treatment with pegylated IFN-alpha plus ribavirin or to postpone treatment for 8 weeks. Prior to randomization and 8 weeks later all subjects will be evaluated with the EAR in their home environments and will undergo TSST, 14 hour diurnal neuroendocrine and immune measurement and overnight sleep polysomnography in the Atlanta Clinical and Translational Science Institute Clinical Interactions Network site at Emory University.